Estimated Population-Level Impact of Pneumococcal Conjugate Vaccines Against All-Cause Pneumonia Mortality Among Unvaccinated in 5 Latin American Countries.

BACKGROUND: Pneumococcal conjugate vaccines (PCVs) provide strong direct protection in children, while limited data are available on their indirect effect on mortality among older age groups. This multicountry study aimed to assess the population-level impact of pediatric PCVs on all-cause pneumonia mortality among children ≥5 years of age, and invasive pneumococcal disease (IPD) cases in Chile. METHODS: Demographic and mortality data from Argentina, Brazil, Chile, Colombia, and Mexico were collected considering the ≥ 5-year-old population, from 2000 to 2019, with 1 795 789 deaths due to all-cause pneumonia. IPD cases in Chile were also evaluated. Time series models were employed to evaluate changes in all-cause pneumonia deaths during the postvaccination period, with other causes of death used as synthetic controls for unrelated temporal trends. RESULTS: No significant change in death rates due to all-cause pneumonia was detected following PCV introduction among most age groups and countries. The proportion of IPD cases caused by vaccine serotypes decreased from 29% (2012) to 6% (2022) among people aged ≥65 years in Chile. DISCUSSION: While an effect of PCV against pneumonia deaths (a broad clinical definition that may not be specific enough to measure indirect effects) was not detected, evidence of indirect PCV impact was observed among vaccine-type-specific IPD cases.

Declines in Pneumonia Mortality Following the Introduction of Pneumococcal Conjugate Vaccines in Latin American and Caribbean Countries.

BACKGROUND: Pneumococcal conjugate vaccines (PCVs) are recommended for use in pediatric immunization programs worldwide. Few data are available on their effect against mortality. We present a multicountry evaluation of the population-level impact of PCVs against death due to pneumonia in children < 5 years of age. METHODS: We obtained national-level mortality data between 2000 and 2016 from 10 Latin American and Caribbean countries, using the standardized protocol. Time series models were used to evaluate the decline in all-cause pneumonia deaths during the postvaccination period while controlling for unrelated temporal trends using control causes of death. RESULTS: The estimated declines in pneumonia mortality following the introduction of PCVs ranged from 11% to 35% among children aged 2-59 months in 5 countries: Colombia (24% [95% credible interval {CrI}, 3%-35%]), Ecuador (25% [95% CrI, 4%-41%]), Mexico (11% [95% CrI, 3%-18%]), Nicaragua (19% [95% CrI, 0-34%]), and Peru (35% [95% CrI, 20%-47%]). In Argentina, Brazil, and the Dominican Republic, the declines were not detected in the aggregated age group but were detected in certain age strata. In Guyana and Honduras, the estimates had large uncertainty, and no declines were detected. Across the 10 countries, most of which have low to moderate incidence of pneumonia mortality, PCVs have prevented nearly 4500 all-cause pneumonia deaths in children 2-59 months since introduction. CONCLUSIONS: Although the data quality was variable between countries, and the patterns varied across countries and age groups, the balance of evidence suggests that mortality due to all-cause pneumonia in children declined after PCV introduction. The impact could be greater in populations with a higher prevaccine burden of pneumonia.

Impact of pneumococcal conjugate vaccine on pneumonia hospitalization and mortality in children and elderly in Ecuador: Time series analyses.

BACKGROUND: Pneumococcal conjugate vaccines (PCV) reduce the burden of invasive pneumococcal disease and pneumonia hospitalizations. However, there is limited evidence of the effect of PCVs on pneumonia mortality in children. It is anticipated that indirect effects resulting from PCV use among children might further reduce the remaining burden of adult pneumococcal disease caused by pneumococcal serotypes contained in PCV. Whether this will result in reduced pneumonia mortality in children and adults is still not known. METHODS: We investigated the impact of PCV on pneumonia hospitalization and mortality in in Ecuador, where PCV was introduced in 2010, considering national data from secondary data sources from 2005 to 2015. Time series analysis using regression models were used to evaluate the decline in the number of all-cause pneumonia hospitalizations and deaths in the period post-PCV introduction. The target populations were children under 5 years and adults aged 50 years and over. Outcomes of interest were hospitalizations and mortality in which the main cause of hospital admission and death, respectively, were coded as ICD10 codes J12-18 (pneumonia). Three different models were fitted. RESULTS: We demonstrate a sizeable impact of PCV in pneumonia hospitalization in children < 1 year (27% reduction, 95%CI 12-42%), and < 5 years of age (33% reduction, 95%CI 11-43%). The estimated impact of PCV in pneumonia mortality was a reduction of 14% in < 1 year (95%CI 0-33%), 10% in < 5 years (95%CI 0-25%), and 22% (95%CI 7-34%) in adults aged 50-64 years. Little evidence of a change was detected in elderly ≥ 65 years. CONCLUSION: This study is the first to report on the impact of PCV in pneumonia morbidity and mortality in children and older adults, being relevant to policy makers and global donors. Findings were consistent when using different models. Additional studies on the indirect effect of PCV in older adults are needed.

Impact of pneumococcal conjugate vaccine uptake on childhood pneumonia mortality across income levels in Brazil, Colombia, and Peru.

Background: Pneumococcal conjugate vaccines (PCVs) have prevented deaths due to pneumonia among children. The effect may differ between higher- and lower-income populations due to various factors, such as differences in the distribution of pneumococcal serotypes, healthcare access, and PCV uptake. This study aims to evaluate an association between increasing PCV coverage and population-level declines in death due to pneumonia and its variation by socioeconomic status of subnational regions. Methods: We analyzed municipality-level mortality data from 2005 and 2015 for children aged 2-23 months in Brazil, Colombia, and Peru. We fit Poisson regression models to estimate the relationship between changes in PCV uptake and deaths due to all-cause pneumonia among subnational regions with different income levels. We controlled for changes unrelated to PCV by using data on non-respiratory deaths over time. Results: Uptake of the third dose of PCV varied across subnational regions and was higher in high-income regions. Higher uptake of PCV was associated with larger declines in pneumonia mortality. This association did not differ by income level of the region in Brazil and Colombia. In Peru, low-income regions observed larger declines in pneumonia deaths, but there was large uncertainty in the difference between the low- and high-income regions. We estimated that, with 90% coverage, there would be 4-38% declines in all-cause pneumonia mortality across income levels and countries. Conclusions: Regions with higher PCV coverage experienced larger declines in pneumonia deaths, regardless of the income level. Having more reliable data on mortality records and vaccine uptake would improve the reliability of vaccine impact estimates.

Effect of Age at Vaccination on Rotavirus Vaccine Effectiveness in Bolivian Infants.

BACKGROUND: Rotavirus vaccines are less effective in developing countries versus developed countries. One hypothesis for this difference in performance is that higher levels of maternal antibodies in developing countries may interfere with vaccine response, suggesting that delayed dosing could be beneficial. The present analysis aims to assess whether rotavirus vaccine effectiveness (VE) varies by age at vaccination during routine use in Bolivia. METHODS: Data were merged from 2 postlicensure evaluations of monovalent rotavirus vaccine (RV1) in Bolivia, where 2 doses of RV1 are recommended at 2 and 4 months of age. For each dose, children were classified as receiving each dose "early," "on-time" or "late." Stratified unconditional logistic regression models were used to estimate VE, using unvaccinated children as the referent. VE was calculated as (1 - odds ratio) × 100%. Models were adjusted for hospital, age and time since RV1 introduction (via including terms for month and year of birth). RESULTS: VE for 2 doses of RV1 tended to be higher in infants receiving the first dose early (VE, 92%; 95% confidence interval: 70%-98%), when compared with infants receiving their first dose on-time [72% (62%-81%)] or late [68% (51%-79%)]. Estimates of VE were not substantially different when comparing children by age at second dose [early: VE, 76% (50%-89%); on-time: VE, 70% (50%-89%); late: VE, 75% (60%, 84%)], including all children. CONCLUSIONS: Our results indicate that early administration may improve VE and support the current World Health Organization recommendations for the RV1 schedule.

Impact of pneumococcal conjugate vaccine in children morbidity and mortality in Peru: Time series analyses.

Streptococcus pneumoniae is the leading cause of bacterial pneumonia, meningitis and sepsis in children worldwide. Despite available evidence on pneumococcal conjugate vaccine (PCV) impact on pneumonia hospitalizations in children, studies demonstrating PCV impact in morbidity and mortality in middle-income countries are still scarce. Given the disease burden, PCV7 was introduced in Peru in 2009, and then switched to PCV10 in late 2011. National public healthcare system provides care for 60% of the population, and national hospitalization, outpatient and mortality data are available. We thus aimed to assess the effects of routine PCV vaccination on pneumonia hospitalization and mortality, and acute otitis media (AOM) and all cause pneumonia outpatient visits in children under one year of age in Peru. We conducted a segmented time-series analysis using outcome-specific regression models. Study period was from January 2006 to December 2012. Data sources included the National information systems for hospitalization, mortality, outpatient visits, and RENACE, the national database of aggregated weekly notifications of pneumonia and other acute respiratory diseases (both hospitalized and non-hospitalized). Study outcomes included community acquired pneumonia outpatient visits, hospitalizations and deaths (ICD10 codes J12-J18); and AOM outpatient visits (H65-H67). Monthly age- and sex-specific admission, outpatient visit, and mortality rates per 100,000 children aged <1year, as well as weekly rates for pneumonia and AOM recorded in RENACE were estimated. After PCV introduction, we observed significant vaccine impact in morbidity and mortality in children aged <1year. Vaccine effectiveness was 26.2% (95% CI 16.9-34.4) for AOM visits, 35% (95% CI 8.6-53.8) for mortality due to pneumonia, and 20.6% (95% CI 10.6-29.5) for weekly cases of pneumonia hospitalization and outpatient visits notified to RENACE. We used secondary data sources which are usually developed for other non-epidemiologic purposes. Despite some data limitations, our results clearly demonstrate the overall benefit of PCV vaccination in Peru.

Effectiveness of the 10-Valent Pneumococcal Conjugate Vaccine (PCV-10) in Children in Chile: A Nested Case-Control Study Using Nationwide Pneumonia Morbidity and Mortality Surveillance Data.

BACKGROUND: The ten-valent pneumococcal conjugate vaccine (PCV10) was introduced into the Chilean National Immunization Program (NIP) in January 2011 with a 3+1 schedule (2, 4, 6 and 12 months) without catch-up vaccination. We evaluated the effectiveness of PCV10 on pneumonia morbidity and mortality among infants during the first two years after vaccine introduction. METHODS: This is a population-based nested case-control study using four merged nationwide case-based electronic health data registries: live birth, vaccination, hospitalization and mortality. Children born in 2010 and 2011 were followed from two moths of age for a period of two years. Using four different case definitions of pneumonia hospitalization and/or mortality (all-cause and pneumonia related deaths), all cases and four randomly selected matched controls per case were selected. Controls were matched to cases on analysis time. Vaccination status was then assessed. Vaccine effectiveness (VE) was estimated using conditional logistic regression. RESULTS: There were a total of 497,996 children in the 2010 and 2011 Chilean live-birth cohorts. PCV10 VE was 11.2% (95%CI 8.5-13.6) when all pneumonia hospitalizations and deaths were used to define cases. VE increased to 20.7 (95%CI 17.3-23.8) when ICD10 codes used to denote viral pneumonia were excluded from the case definition. VE estimates on pneumonia deaths and all-cause deaths were 71.5 (95%CI 9.0-91.8) and 34.8 (95% CI 23.7-44.4), respectively. CONCLUSION: PCV10 vaccination substantially reduced the number of hospitalizations due to pneumonia and deaths due to pneumonia and to all-causes over this study period. Our findings also reinforce the importance of having quality health information systems for measuring VE.

Systematic documentation of new vaccine introduction in selected countries of the Latin American Region.

BACKGROUND: Countries in Latin America were among the first developing countries to introduce new vaccines, particularly rotavirus (RV) and pneumococcal conjugate vaccines (PCVs), into their national immunization schedules. Experiences and lessons learned from these countries are valuable to donors, immunization partners, and policy makers in other countries wishing to make informed decisions on vaccine introduction. OBJECTIVES: In order to enhance knowledge and promote understanding of the process of new vaccine introduction in the Latin American Region, with particular focus on RV and PCV, we conducted a systematic qualitative assessment. We evaluated the decision-making process, documented the structure in place, and reviewed key factors pertaining to new vaccine introduction. These include country morbidity and mortality data available prior to vaccine introduction, funding sources and mechanisms for vaccine introduction, challenges of implementation, and assessment of vaccine impact. METHODS: From March 2010 to April 2011, we evaluated a subset of countries that had introduced RV and/or PCV in the past five years through interviews with key informants at the country level and through a systematic review of published data, gray literature, official technical documents, and country-specific health indicators. Countries evaluated were Bolivia, Brazil, Nicaragua, Peru, and Venezuela. RESULTS: In all countries, the potential of new vaccines to reduce mortality, as established by Millennium Development Goal 4, was an important consideration leading to vaccine introduction. Several factors-the availability of funds, the existence of sufficient evidence for vaccine introduction, and the feasibility of sustainable financing-were identified as crucial components of the decision-making process in the countries evaluated. CONCLUSIONS: The decision making process regarding new vaccine introduction in the countries evaluated does not follow a systematic approach. Nonetheless, existing evidence on efficacy, potential impact, and cost-effectiveness of vaccine introduction, even if not local data, was important in the decision making process for vaccine introduction.

Sistema de vigilancia de rotavirus en hospitales centinelas en Chile / Rotavirus surveillance system in Chilean sentinel hospitals

OBJETIVO: las diarreas son una de las principales causas de morbilidad y mortalidad en el mundo. En Chile, su vigilancia es una prioridad, muy en particular las causadas por rotavirus para conocer su epidemiología, incluidos los serotipos circulantes y detectar brotes oportunamente. MÉTODOS: se implementó un sistema de vigilancia en 8 hospitales pedißtricos, considerados sitio centinela por cubrir 62 por ciento de la población menor de 5 años de las regiones Metropolitana, Valparaíso y Bio-Bio. Se utilizaron las definiciones de caso estandarizadas por la Organización Mundial de la Salud. Las muestras fueron analizadas en los laboratorios del Instituto de Salud Pública con la técnica inmunoensayo enzimßtico en el formato de ELISA. El sistema se basa en un formulario electrónico en línea, sobre plataforma de programación PHP versión 5.2.6, diseñado para creación de páginas web dinßmicas, accesible mediante clave o password de los terminales del centro centinela, de la Secretaria Regional Ministerial de Salud e Instituto de Salud Pública, donde se introducen las variables semanal y mensualmente de forma definitiva. El anßlisis se realiza en el programa estadístico Epinfo-2000. RESULTADOS: en 8 meses de vigilancia, se estudiaron 599 muestras de deposiciones, 164 positivas a rotavirus (27,4 por ciento), tasa de 0,2 por 1 000 habitantes. Al sexo masculino pertenece 56 por ciento, el menor de 2 años es el más afectado (69 por ciento). CONCLUSIONES: la implementación del sistema de vigilancia centinela para rotavirus constituye una herramienta útil para conocer el comportamiento de esta enfermedad y contribuir a la toma de decisiones por los programas nacionales de salud(AU)

OBJECTIVE: diarrheas are one of the main causes of morbidity and mortality worldwide. In Chile, diarrhea surveillance is a priority, particularly those caused by rotavitus, in order to find out their epidemiology including circulating serotypes and to promptly detect possible outbreaks. METHODS: a surveillance system was implemented in 8 pediatric hospitals considered as sentinel sites because they cover 62 percent of the under 5 years-old population from Metropolitana, Valparaiso and Bio-Bio regions. The standardized case definitions of the World Health Organization were used. The sample analysis was based on ELISA method in the Public Health Institute laboratories. The surveillance system is based on an online electronic form supported on PHP platform, 5.2.6 version, designed to create dynamic and accessible webpages through passwords from the sentinel center terminals of the Regional Ministerial Department of Health and the Public Health Institute; the variables are weekly and monthly introduced. The statistical analysis is carried out through Epinfo-2000. RESULTS: five hundred and ninety nine fecal samples were analyzed in eight months; 164 of them were positive to rotavirus (27.4 percent) for a rate of 0.2 per 1000 pop. Fifty six percent were males whereas under 2 years-old group was the most affected (69 percent). CONCLUSIONS: the implementation of the sentinel rotavirus surveillance system is a useful tool for the analysis of this disease behavior and for decision-making in the health national programs(AU)

Sistema de vigilancia de rotavirus en hospitales centinelas en Chile / Rotavirus surveillance system in Chilean sentinel hospitals

OBJETIVO: las diarreas son una de las principales causas de morbilidad y mortalidad en el mundo. En Chile, su vigilancia es una prioridad, muy en particular las causadas por rotavirus para conocer su epidemiología, incluidos los serotipos circulantes y detectar brotes oportunamente. MÉTODOS: se implementó un sistema de vigilancia en 8 hospitales pedißtricos, considerados sitio centinela por cubrir 62 por ciento de la población menor de 5 años de las regiones Metropolitana, Valparaíso y Bio-Bio. Se utilizaron las definiciones de caso estandarizadas por la Organización Mundial de la Salud. Las muestras fueron analizadas en los laboratorios del Instituto de Salud Pública con la técnica inmunoensayo enzimßtico en el formato de ELISA. El sistema se basa en un formulario electrónico en línea, sobre plataforma de programación PHP versión 5.2.6, diseñado para creación de páginas web dinßmicas, accesible mediante clave o password de los terminales del centro centinela, de la Secretaria Regional Ministerial de Salud e Instituto de Salud Pública, donde se introducen las variables semanal y mensualmente de forma definitiva. El anßlisis se realiza en el programa estadístico Epinfo-2000. RESULTADOS: en 8 meses de vigilancia, se estudiaron 599 muestras de deposiciones, 164 positivas a rotavirus (27,4 por ciento), tasa de 0,2 por 1 000 habitantes. Al sexo masculino pertenece 56 por ciento, el menor de 2 años es el más afectado (69 por ciento). CONCLUSIONES: la implementación del sistema de vigilancia centinela para rotavirus constituye una herramienta útil para conocer el comportamiento de esta enfermedad y contribuir a la toma de decisiones por los programas nacionales de salud.

OBJECTIVE: diarrheas are one of the main causes of morbidity and mortality worldwide. In Chile, diarrhea surveillance is a priority, particularly those caused by rotavitus, in order to find out their epidemiology including circulating serotypes and to promptly detect possible outbreaks. METHODS: a surveillance system was implemented in 8 pediatric hospitals considered as sentinel sites because they cover 62 percent of the under 5 years-old population from Metropolitana, Valparaiso and Bio-Bio regions. The standardized case definitions of the World Health Organization were used. The sample analysis was based on ELISA method in the Public Health Institute laboratories. The surveillance system is based on an online electronic form supported on PHP platform, 5.2.6 version, designed to create dynamic and accessible webpages through passwords from the sentinel center terminals of the Regional Ministerial Department of Health and the Public Health Institute; the variables are weekly and monthly introduced. The statistical analysis is carried out through Epinfo-2000. RESULTS: five hundred and ninety nine fecal samples were analyzed in eight months; 164 of them were positive to rotavirus (27.4 percent) for a rate of 0.2 per 1000 pop. Fifty six percent were males whereas under 2 years-old group was the most affected (69 percent). CONCLUSIONS: the implementation of the sentinel rotavirus surveillance system is a useful tool for the analysis of this disease behavior and for decision-making in the health national programs.